COMPARTMENTALIZED LUNG CYTOKINE RELEASE IN RESPONSE TO INTRAVASCULAR AND ALVEOLAR ENDOTOXIN CHALLENGE

Lung cytokine generation has been implicated in pulmonary injury and s ystemic inflammatory responses. In buffer-perfused rabbit lungs, intra vascular endotoxin (10 ng/ml perfusate; total amount 7 mu g) provoked the liberation of 212,100 +/- 119,700 mu g tumor necrosis factor-alpha (TNF-alpha) into the vascular space within 3 h. This was augmented to 3,564,400 +/- 1,285,900 pg in the presence of 1% serum. Bronchoalveol ar lavages demonstrated the absence of buffer-admixed endotoxin and tr ansition of only minor fractions of the vascular TNF-alpha load into t he alveolar space. Aerosolization of 22 mu g endotoxin liberated 824,4 00 +/- 48,750 pg TNF-alpha into the alveolar compartment, which was ev en increased to 16,980,000 +/- 6,066,350 pg on co-nebulization of seru m. No endotoxin and only minor amounts of the alveolar TNF-alpha burde n spilled over into the vascular compartment. Vascular pressures and l ung vascular permeability did not change. We conclude that both intrav ascular and alveolar endotoxin challenge provokes excessive lung TNF-a lpha generation, amplified manyfold in the presence of small serum qua ntities. For both routes of application, however, the cytokine respons es were found to be largely compartmentalized under the given conditio ns of integer lung barrier properties.